Ovarian cancer personal story

During my 29 years of work as a hospital pathologist, I conservatively estimate I assumed the responsibility for diagnosing over 75,000 malignant neoplasms and followed the clinical course of many of those cases. That experience was rewarding. It gave me a clear sense of the biology of diverse cancers, as well as the clinical outcomes achievable with the mainstream therapies. During the last two decades, my colleagues at the Institute and I participated in the clinical management of over 2,000 cases of cancer. That experience has been disconcerting, largely because it was not possible to clearly delineate the long-term efficacy of our integrative therapies. Most of those patients concurrently received immunosuppressive therapies--chemotherapy, radiotherapy and others--that countered the integrative oxystatic therapies which we prescribed. Another common problem has been the financial burden of integrative therapies on patients, since insurance carriers nearly always refuse to cover such therapies, seriously compromising the continuity of care.

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Fortunately, there has also been a subgroup of about 60 self-selected, well-informed, highly-motivated, and strong-willed individuals who assumed the primary responsibility of the control of their own cancers. They have been under our care for two to twelve years. Though limited, my experience with this small subgroup has been richly rewarding. I write this article to share my views of the biology of cancer and responses to integrative therapies based on insights they gave me, as well as on personal pathologic, clinical, and research findings. In my effort, I have looked at the problems of cancer through the prism of oxygen homeostasis because, as I explain below, oxygen drives all host defense responses to malignant neoplasms. From that perspective, I succinctly state my conclusion as follows:

The long-term outcome in unresectable cancer is primarily determined by how well oxygen homeostasis can be achieved and maintained. The benefits of soy and other phytofactors, with or without therapies that modify specific molecular and genetic pathways, are often substantial in the sense that such therapies can alter the behavior of cancer cells for variable periods of time until oxystatic therapies begin to take hold.

Oxidative Injury and Cancer

In 1995, I put forth my view that accelerated oxidative injury is the common denominator in all known factors implicated in carcinogenesis. Furthermore, unrelenting oxidative stress from any and all causes is the single most important mechanism for sustaining and perpetuating the malignant cellular replication. (1) In 2001, looking through the prism of oxygen homeostasis, I extended that hypothesis and offered the following definition of cancer:

Cancer is destructive behavior of cells incited and perpetuated by many factors that cumulatively lead to anomalous oxygen signaling. It has six other principal characteristics: (1) respiratory-to-fermentative (RTF) shift in ATP production; (2) production of prodigious quantities of organic acids--lactic acid and others; (3) creation of a cocoon of coagulated proteins around malignant cells to exclude functioning host immune cells and their soluble defense molecules; (4) uncontrolled cellular replication that disrupts local tissue architecture; (5) colonization of distant tissues in which the destructive behavior of neoplastic cells continues; and (6) under certain conditions, a cancer cell can be coaxed to alter its behavior. (2)

Coaxed to alter its behavior! From a clinical standpoint, this last attribute of cancer, in my view, should be accepted as the singular aspect of cancer of interest, both for the patient and the practitioner.

Except when early surgical excision can extirpate the cancer in toto, the long-term outcome with cancer therapies depends on how effectively oxygen homeostasis is achieved and preserved. This statement may raise some eyebrows. But this conclusion seems inescapable to me in light of personal pathologic, clinical, and research observations.

There are three treatment approaches to cancer in oncology today: (1) chemotherapy; (2) radiotherapy; and (3) newer agents that target one or more of the signaling pathways in host defenses. All three approaches seek to remove or destroy every cancer cell in the body of the patient. Notwithstanding exuberance of the oncology community, the real story of progress in cancer treatment has been--and continues to be--dismal. Consider the following quote from a 1997 report concerning national cancer statistics in The New England Journal of Medicine: "In 1986, we concluded that some 35 years of intense effort focused largely on improving treatment must be judged a qualified failure. Now, with 12 more years of data and experience, we see little reason to change that conclusion." (3)

The approach of altering the behavior of a cancer cell by focusing on issues of oxygen homeostasis, by contrast, has a different goal: to so alter the host conditions in a person with cancer that the cancer cells can be coaxed to behave in a nonmalignant fashion and/or to facilitate destruction of cancer cells by host defenses.

Thiosphaera pantotropha

Thiosphaera pantotropha is a metabolic two-timer--highly skillful in extraction of energy from sewage when oxygen is essentially absent, as well as when it is available. (4-6) First identified in 1983 in sewage plants, T. pantotropha energizes itself by robust metabolism of sulfides and thiosulfate, using nitric oxides instead of oxygen. When oxygen is available, it switches to aerobic metabolism and efficiently extracts energy from a wide array of inorganic substrates by aerobic respiration. Evidently, the bug is wise in the ways of managing its genetic pool to serve dual roles under changing conditions of oxygen availability. Indeed, in sewage plants, bursts of oxygen are introduced periodically to invigorate this microbe for enhanced sewage treatment. It is noteworthy in this context that there are many other microbial metabolic two-timers.

A cancer cell, like T. pantotropha, is also a metabolic two-timer, but with a difference: it survives in the presence of oxygen but thrives in its absence. The singular challenge in the field of cancer--in my view--is this: Can we create oxygen conditions in the body that coax a cancer cell to relinquish its infatuation with the respiratory-to-fermentative (RTF) shift, and revert back to its human respiratory mode of ATP generation with a fermentative-to-respiratory (FTR) shift? In other words, can the predominantly glycolytic metabolism mode of a cancer cell be switched to the physiologic respiratory ATP energetics of a healthy cell, fundamentally altering its energetic behavior? That is a tantalizing possibility. But, what may be realistically hoped for here? I see limited value of chemotherapeutic agents in this endeavor. By contrast, in the future I see much potential in the clinical benefits of antibodies directed against signaling molecules that sustain and perpetuate malignant cell replication. Some notable examples of such drugs are: (1) imatinib (Gleevec, a protein-tyrosine kinase inhibtor) Bcr-Ab1 tyrosine kinase; (2) gefitinib (Iressa, an inhibitor of intracellular phosphorylation of several tyrosine kinases) which binds epidermal growth factor; (3) trastuzumab (Herceptin, a DNA-derived humanized monoclonal antibody) which binds with the extracellular domain of the human epidermal growth factor receptor 2 protein (HER2); (4) rituximab (Rituxin, a chimeric murine/human monoclonal antibody) which binds to CD20 antigens; (5) Avastin which targets angiogenesis; and others.

Altering the Behavior of Cancer Cells: Fermentative-to-Respiratory (FTR) Shift

Returning to the core issue of the possibility of coaxing cancer cells to a fermentative-to-respiratory (FTR) shift--return from glycolytic metabolism back to physiological respiratory ATP production--I cite the example of well-differentiated adenocarcinoma of endometrium that arises in severe atypical endometrial hyperplasia in young anovulatory females. Pregnancy in many such cases so alters the endometrial microecology that no sign of endometrial malignancy can be seen years later. Evidently, in such cases conception does not physically eradicate every single cancerous endometrial cell. Rather, gestation alters the behavior of malignant cells.

The FTR shift, of course, is also seen in other types of cancer. I have been most impressed by a group of 28 patients with biopsy-proven